Metabolite Profiling of Cerebrospinal Fluid Derived from MS Patients (P5.238)

Objective: To identify unique metabolic determinants in cerebrospinal fluid (CSF) of patients with progressive MS. Background: Disease progression in MS is poorly understood and there is a need to investigate the biochemical abnormalities specifically associated with progressive MS. Design/methods: CSF was obtained from healthy controls (n=15, untreated secondary progressive MS (SPMS; N=15)and untreated primary progressive MS (PPMS; N=15) patients with informed consent under an IRB-approved protocol. CSF was analyzed on the GC/MS and LC/MS/MS platforms by Metabolon (Durham, NC. Results: Fifty metabolites were found to be significantly altered in the MS cohort as compared to controls. Additionally, the analysis revealed the differential metabolite profiles of PPMS and SPMS populations (18 with a p≤0.05). These notably included changes in metabolites related to carbohydrate metabolism, specifically through glycolysis and the pentose phosphate pathway (PPP). In particular, increased levels of the biochemical indicator of glucose utilization lactate, as well as elevations in several pentose sugars that may be obtained from the diet or synthesized through the PPP (ribulose, ribitol, xylonate, xylose, xylitol, arabinose, and threitol) were noted in both MS patient groups. Moreover, higher levels of metabolites involved in alternative pathways of glucose utilization, such as sorbitol and fructose, along with increased levels of the sugar alcohol mannitol and its derivative mannose were observed in the MS groups. Arginine metabolism was also found significantly affected with changes in creatine and creatinine as well as elevations in two biochemical markers of extracellular matrix (ECM) remodeling namely trans-4-hydroxyproline) and pro-hydroxy-pro, especially in PPMS patients. This indicates a differential contribution of ECM remodeling in PPMS disease. The study also found changes in the neuroactive amino acids, and additional “isolated” metabolites. Conclusion This study revealed perturbations in the CSF metabolome that were both consistent and different when comparing patients with PPMS or SPMS and warrant further investigation. Disclosure: Dr. Blemur has nothing to disclose. Dr. Mir has nothing to disclose. Dr. Sadiq has nothing to disclose.